Chemotherapy Antineoplastic Agents

Front 1

Cyclophosphamide Pharmacokinetics:

Back 1

The parent drug is not an active cytotoxic compound.It is converted to acrolein and phosphoramide mustard. Phosphoramide mustard produces alkylation with DNA.

Front 2

Cyclophosphamide
Clinical Applications:

Back 2

It is used in treating lymphomas and many
solid tumors including breast

Front 3

Cyclophosphamide
Toxicity:

Back 3

Urinary: Acrolein is excreted in the urine and may cause hemorrhagic cystitis a severe toxicity to the bladder.
Prophylaxis:With very high dosages mercaptoethane sulfonate (MESNA) may be given to prevent damage to the bladder

Front 4

Cyclophosphamide
Pharmacokinetics:

Back 4

Cyclophosphamide is well absorbed after oral
administration and is available in tablet and
parenteral formulations.
• The major site of clearance is the liver

Front 5

Ifosfamide
Pharmacokinetics:

Back 5

• Like cyclophosphamide, ifosfamide is activated by
hepatic microsomal enzymes and eventually is
converted to acrolein and ifosforamic mustard.
ifosfamide responds much more slowly to
the activating enzyme, and an equivalent dose is
three to four times that of cyclophosphamide.
• As a result more acrolein is produced and bladder
toxicity is greater.

Front 6

Ifosfamide
Clinical Applications:
Note:

Back 6

FDA approved for treatment
of relapsed germ cell testicular cancer.
Believed to be more efficacious when given
daily for 4-5 days usually as a continuous infusion

Front 7

Ifosfamide
Toxicity:

Back 7

Urinary: For ifosfamide to be safely administered in
therapeutic doses it must be administered with a
uroprotectant, such as MESNA.

Front 8

MESNA
Mechanisim:

Back 8

Contains a free sulfhydryl group that binds to the acrolein in the urine to form a nontoxic compound in the bladder.

Front 9

MESNA
Administration:

Back 9

Is very effective in preventing hemorrhagic cystitis but is not helpful in alleviating it once it has occurred. Therefore, giving it prophylactically is very important.

The solution tastes like rotten eggs.

Front 10

Ifosfamide
Toxicity:
Hematologic

Back 10

Myelosuppression is a major dose limiting toxicity.

Front 11

Ifosfamide
Neurologic Toxicity:

Back 11

Occurs more commonly
in one day regimens and in renal impairment as a
result of the toxic metabolite choloracetaldehyde.
-Methylene blue is given as an antidote and the ifosfamide is usually stopped.

Front 12

Melphalan
Clinical Applications:

Back 12

Melphalan is FDA approved for
multiple myeloma
Also used in isolated limb perfusion (for melanoma)
and in induction regimens before bone marrow/stem cell transplants.

Front 13

Melphalan
Pharmacokinetics:

Back 13

An oral tablet form,Food slows its absorption.

Undergoes spontaneous hydrolysis in the blood stream.

Front 14

Chlorambucil
Clinical Applications:

Back 14

Given orally for treating chronic lymphocytic leukemia, lymphomas, and multiple myeloma. (liquid cancers)

Front 15

Chlorambucil
Pharmacokinetics:

Back 15

Oral chlorambucil appears to be absorbed more completely (85-90%) and rapidly than oral melphalan.